Trombocita aggregáció gátló kezelés hatékonyságának genetikai és metodikai aspektusai koronária intervención átesett betegek körében

Coronary artery disease (CAD) is known to be a very heterogeneous disease of multifactorial origin affecting millions world-wide and being the top leading cause of death among the middle-aged population. The development of percutaneous coronary intervention (PCI) has revolutionized the treatment of ischaemic heart disease. However, despite the efforts some short and longer term complication has been realized; acute stent thrombosis (ST) and instent restenosis (ISR), both resulting in target-vessel failure after PCI, still occur. Significant interindividual differences in response to anti-platelet therapy have recently been recognized with supposed environmental, clinical, pharmacokinetic and genetic background. While lack of standardization in platelet function assays and paucity of well defined cut off values represent further difficulties of the subject. The circumstances that individuals may have different needs for anti-platelet action as well as different risk for bleeding, point toward the need for an individualized therapeutic regime

A hangulatstabilizáló gyógyszerek (lítium, valproinsav, karbamazepin) hatásai a kalcium ionok által közvetített intracelluláris jelátvitelre = Effects of mood stabilizer drugs (lithium, valproic acid, carbamazepine) on the calcium ion mediated intracellular signal transduction

A lítium bipoláris betegek kezelésére használt gyógyszer, azonban pontos hatásmechanizmusa máig nem tisztázott. Korábbi kutatásokból ismert, hogy a lítium gátolja a foszfoglukomutázt, mely a galaktóz metabolizmus egyik kulcsenzime. Mivel a galaktóz tápanyagforrásul szolgálhat, valamint metabolitjai elengedhetetlen építőkövei a glikoproteineknek, glikolipideknek, tanulmányunkban a lítium galaktóz metabolizmusra kifejtett hatását vizsgáltuk, valamint ezen hatások celluláris válaszreakcióit. Munkánk eredményeként megállapítottuk, hogy a lítium kezelés jelentősen befolyásolja a galaktóz metabolizmust. Ennek következtében olyan poszt-transzlációs fehérje módosulások jöhetnek létre, melyek hypoglikémiás állapotra hasonlítanak. Ezzel magyarázatot találtunk arra a kérdésre, hogy miért aktiválódik az unfolded protein response galaktózon növesztett, lítiummal kezelt sejtekben. | Lithium is a known mood stabilizer in the therapy of bipolar disorders however its exact molecular mechanism is not clarified yet. It was shown earlier that lithium inhibits phosphoglucomutase, one of the key enzyme of galactose metabolism. Since galactose is an important nutrient resource and its metabolites are essential for glycoprotein, glycolipid synthesis, inn this study we examined the effect of lithium on galactose metabolism and subsequent changes in the protein post-translational modification. We demonstrated that lithium significantly influences galactose metabolism and due to this, causing disturbances in the post-translational protein modification similar to hypoglycemic conditions. This process could be the missing link that leads to UPR activation in cells grown on galactose and treated by lithium

High Prevalence of Non-Vaccinated Oncogenic Human Papillomavirus Genotypes in High-Grade Squamous Intraepithelial Lesions of the Cervix: Thought-Provoking Results of a Detailed HPV Genotype Analysis

Identification of HPV infection is usually performed on cytological specimens, despite the often transient virus types. HPV profile analysis of pathologically confirmed lesions can also be performed on formalin-fixed paraffin-embedded (FFPE) cone samples and should be taken as standard during follow-up. We compared HPV profiles of cytological and FFPE specimens of women diagnosed with HSIL. Archived PAP smears and FFPE cones from 49 patients were processed. For genotyping, the HPV Direct Flow CHIP test was used. All samples were positive. HPV profile agreement of the two sample types was 84.16–100%. Mono-infections occurred in 12.24% and 61.22% in PAP smears and FFPE specimens, respectively; while multi-infections were detected in 87.76% and 38.78%, respectively. The most abundant genotypes were HPVs 16, 31, and 51/33. Of all infections, 56.25% and 64.93% were caused by nonavalent vaccinated type (VT) HPVs; while 50.69% and 38.96% belonged to non-nonavalent VT HPVs, in PAP smears and FFPE specimens, respectively. Our results confirmed the importance of HPV genotyping of FFPE cone samples. We also confirmed a remarkable presence of non-vaccinated HPV types in HSIL cases indicating the importance of vaccine development

Wide Spectrum Analysis of Human Papillomavirus Genotypes in External Anogenital Warts

External anogenital warts (EGW) are primarily associated with the low-risk human papillomavirus (HPV) genotypes 6 and 11, though coinfection with other low-risk and oncogenic high-risk HPV genotypes also occurs. Although there have been many studies on HPV-associated disease, the prevalence of HPV genotypes associated with EGW is not well characterized. The objective of our retrospective study was to determine the prevalence of HPV genotypes among patients diagnosed with EGW in the south-west of Hungary. Archived formalin-fixed paraffin-embedded tissues from 94 patients were processed in our study. HPV genotypes were determined, applying HPV Direct Flow CHIP test. The overall prevalence of HPV DNA in the EGW samples was 100%, yielding 131 infections among the 94 samples. Of these cases, 72.3% were mono while 27.6% were multi-infections. Out of the 131 infections, the cumulative prevalence of HPV 6 and 11 was 71%. A total of 98.9% of the samples were carrying at least one of these genotypes, while 19.1% of the cases occurred with at least one high-risk genotype. Data from our study could provide invaluable information concerning the prevalence of HPV types among patients with EGW, enabling improved assessment of the actual and future efficacy of vaccination programs, vaccine development, and forecast changes in infection patterns

High Prevalence of Non-Vaccinated Oncogenic Human Papillomavirus Genotypes in High-Grade Squamous Intraepithelial Lesions of the Cervix: Thought-Provoking Results of a Detailed HPV Genotype Analysis

Identification of HPV infection is usually performed on cytological specimens, despite the often transient virus types. HPV profile analysis of pathologically confirmed lesions can also be performed on formalin-fixed paraffin-embedded (FFPE) cone samples and should be taken as standard during follow-up. We compared HPV profiles of cytological and FFPE specimens of women diagnosed with HSIL. Archived PAP smears and FFPE cones from 49 patients were processed. For genotyping, the HPV Direct Flow CHIP test was used. All samples were positive. HPV profile agreement of the two sample types was 84.16–100%. Mono-infections occurred in 12.24% and 61.22% in PAP smears and FFPE specimens, respectively; while multi-infections were detected in 87.76% and 38.78%, respectively. The most abundant genotypes were HPVs 16, 31, and 51/33. Of all infections, 56.25% and 64.93% were caused by nonavalent vaccinated type (VT) HPVs; while 50.69% and 38.96% belonged to non-nonavalent VT HPVs, in PAP smears and FFPE specimens, respectively. Our results confirmed the importance of HPV genotyping of FFPE cone samples. We also confirmed a remarkable presence of non-vaccinated HPV types in HSIL cases indicating the importance of vaccine development

Multidrogrezisztencia-vizsgálatok krónikus lymphoid leukaemiában = Multidrug resistance in chronic lymphocytic leukemia

Az utóbbi években krónikus lymphoid leukaemiában új prognosztikai faktorok vizsgálata került a figyelem középpontjába. A citogenetikai eltérések, az immunglobulin-nehézlánc génmutációs státusza, a CD38- és ZAP70-expresszió mind a közelmúltban megismert prognosztikus faktorok, de kevés az adat a multidrog-rezisztencia jelentőségéről. Célok: A tanulmány célja genetikai, expressziós és funkcionális szinten jellemezni 82 krónikus lymphoid leukaemiában szenvedő beteg multidrog-rezisztenciájának sajátosságait, és vizsgálni azok összefüggését a betegek túlélésével és a kezelésre adott válasszal. Módszerek: a szerzők 66 betegnél vizsgálták az MDR-1 gén ben – Light Cycler Real Time PCR segítségével meghatározott – „Single Nucleotid Polymorphism” sajátosságot, amely irodalmi adatok szerint a P-glikoprotein expresszióját befolyásolja. Összesen 82 betegnél áramlási citometria során anti-P-glikoprotein monoklonális antitest segítségével a P-glikoprotein- expresszió t, az ún. calcein-verapamil teszttel pedig a multidrog-rezisztencia funkcióját vizsgálták. A kezelésre adott választ 35 betegnél vizsgálták, a statisztikai elemzésnél Fischer-tesztet alkalmazva. A túlélési analízist a teljes beteganyagon elvégezték ( n = 82, Log-rank-teszt). Eredmények: Az irodalmi adatokkal ellentétben a szerzők nem találtak korrelációt a vizsgált három multidrogrezisztencia-teszt között. A kezelésre adott választ vizsgálva 35 kezelt betegből 13 nonrespondernek, 22 pedig respondernek bizonyult. A P-glikoprotein-pozitív fenotípusú esetek ( n = 9) 89%-ban klinikailag nonrespondernek bizonyultak (9 P-glikoprotein-pozitív krónikus lymphoid leukaemiás beteg közül 8 nonresponder volt), a P-glikoprotein-negatív esetek ( n = 26) pedig 80%-ban jó terápiás választ mutattak (26 P-glikoprotein-negatív beteg közül 21 responder) ( p < 0,001). Az átlagos várható túlélésben is jelentős, bár nem szignifikáns ( p = 0,106) különbséget észleltek (84 vs 203 hónap). Következtetések: A vizsgált három laboratóriumi paraméter közül a P-glikoprotein sejtfelszíni jelenléte a leginkább releváns adat krónikus lymphoid leukaemiában a kemorezisztencia előjelzésére és a túléléssel kapcsolatban is prognosztikai faktorként értékelhető. | Introduction: New prognostic factors discovered in chronic lymphocytic leukemia have recently got into the center of clinical interest. While the predictive value of cytogenetical abnormalities, immunglobulin heavy chain gene mutation status, CD38 and ZAP70 expression is already well known, the significance of multidrog resistance in chronic lymphocytic leukemia is not well characterized. Aims: The goal of this study was to characterize the multidrug resistance features in 82 patients with chronic lymphocytic leukemia at the genetical, expression- and functional level and to compare it with the patient’s clinical behavior (survival and response to therapy). Methods: Light Cycler Real Time PCR based „Single Nucleotide Polymorphism” analysis of the MDR1 gene, as a biological predictor of the expression level of P-glycoprotein was tested in 66 patients with chronic lymphocytic leukemia. P-glycoprotein expression and MDR-function was detected in 82 cases by flow cytometry (by use of anti-P-glycoprotein monoclonal antibody and calcein-verapamil functional test). Response to therapy was analyzed by statistical Fisher-test in the treated 35 patients. The survival analysis (Log-rank test) was performed on the whole population ( n = 82). Results: No significant correlation was found between the three levels of multidrug resistance (genetics, phenotype, function) in our patients with chronic lymphocytic leukemia. P-glycoprotein positive cases ( n = 9) were predominantly non-responders (8/9, 89%). There must be, however, other mechanisms causing non-response (total non-responders: 13/35 treated cases). Most of P-glycoprotein negative CLL patients ( n = 26) responded well (21/26, 80%) to chemotherapy (responders: 22/35 treated CLL) ( p < 0,001). The tendency was the same in the average expected survival rate between P-glycoprotein positive and negative patients (84 vs 203 mounths) but the difference was not significant ( p = 0,106). Conclusions: This study proved the clinical prognostic significance of P-glycoprotein expression of leukaemic cells predicting the chemotherapy response and partially estimating the general survival of patients suffering from chronic lymphocytic leukemia

Loss-of-Function Variants in a Hungarian Cohort Reveal Structural Insights on TSH Receptor Maturation and Signaling

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